Copper-catalysed ligation of azides and acetylenes

Abstract

A copper catalyzed click chemistry ligation process is employed to bind azides and terminal acetylenes to provide 1,4-disubstituted 1,2,3-triazole triazoles. The process comprises contacting an organic azide and a terminal alkyne with a source of reactive Cu(I) ion for a time sufficient to form by cycloaddition a 1,4-disubstituted 1,2,3-triazole. The source of reactive Cu(I) ion can be, for example, a Cu(I) salt or copper metal. The process is preferably carried out in a solvent, such as an aqueous alcohol. Optionally, the process can be performed in a solvent that comprises a ligand for Cu(I) and an amine.

What is claimed is: 
     
       1. A copper catalyzed process for preparing a 1,4-disubstituted 1,2,3-triazole comprising:
 contacting an organic azide and a terminal alkyne with Cu(I) ion in the presence of a ligand for Cu(I) to form a 1,4-disubstituted 1,2,3-triazole compound; wherein the ligand for Cu(I) is selected from the group consisting of a nitrile, an alcohol, and a combination thereof. 
 
     
     
       2. The process of  claim 1  wherein the ligand for Cu(I) comprises an alcohol. 
     
     
       3. The process of  claim 1  wherein the ligand for Cu(I) comprises a nitrile. 
     
     
       4. The process of  claim 3  wherein the nitrile comprises acetonitrile. 
     
     
       5. The process of  claim 1  wherein the azide and alkyne are contacted in equimolar amounts. 
     
     
       6. A copper catalyzed process for preparing a 1,4-disubstituted-1,2,3-triazole comprising contacting a solution of an organic azide and a terminal alkyne with Cu(I) ion in the presence of a ligand for Cu(I) to form a 1,4-disubstituted-1,2,3-triazole compound, wherein the ligand is selected from the group consisting of an alcohol, a nitrile and a combination thereof. 
     
     
       7. The process of  claim 6  wherein the ligand for Cu(I) comprises an alcohol. 
     
     
       8. The process of  claim 6  wherein the ligand for Cu(I) comprises a nitrile. 
     
     
       9. The process of  claim 8  wherein the nitrile comprises acetonitrile. 
     
     
       10. The process of  claim 6  wherein the azide and alkyne are contacted in equimolar amounts. 
     
     
       11. The process of  claim 6  wherein the solution is an aqueous solution. 
     
     
       12. The process of  claim 6  wherein the solution comprises an alcohol as a solvent. 
     
     
       13. The process of  claim 6  wherein the solution comprises acetonitrile as a solvent. 
     
     
       14. A copper catalyzed process for preparing a 1,4-disubstituted-1,2,3-triazole comprising contacting a solution of an organic azide and a terminal alkyne with a catalytic amount of Cu(I) ion to form a 1,4-disubstituted-1,2,3-triazole compound; wherein the solution also comprises a ligand for Cu(I) selected from the group consisting of a nitrile, a nitrite, an isonitrile, an amine, a carboxylate, a halide, an alcohol, a thiol, and a combination thereof. 
     
     
       15. The process of  claim 14  wherein the solution is an aqueous solution. 
     
     
       16. The process of  claim 14  wherein the solution comprises an alcohol as a solvent. 
     
     
       17. The process of  claim 14  wherein the solution comprises acetonitrile as a solvent.